Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000628987 | SCV000749897 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-30 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 525020). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 31737537). This variant is present in population databases (rs776035548, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 93 of the TNNI3 protein (p.Leu93Pro). |
| Color Diagnostics, |
RCV001179127 | SCV001343734 | uncertain significance | Cardiomyopathy | 2019-06-12 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 93 of the TNNI3 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/242490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| All of Us Research Program, |
RCV000628987 | SCV004819086 | uncertain significance | Hypertrophic cardiomyopathy | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 93 of the TNNI3 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/242490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004678770 | SCV005174023 | uncertain significance | Cardiovascular phenotype | 2024-03-27 | criteria provided, single submitter | clinical testing | The p.L93P variant (also known as c.278T>C), located in coding exon 5 of the TNNI3 gene, results from a T to C substitution at nucleotide position 278. The leucine at codon 93 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |